Inhibitory Effects of Non-steroidal Anti-inflammatory Drugs on Superoxide Generation

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Effects of non-steroidal anti-inflammatory drugs (NSAID : amfenac sodium, diclofenac sodium, indomethacin and ketoprofen) on the generation of superoxide anion (O^-_2) by isolated rat polymorphonuclear leukocytes (PMN) were studied spectrophotometrically using cytochrome c. The effects of these drugs were also studied on O^-_2 production by the xanthine-xanthine oxidase and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-NADPH oxidase systems.Amfenac sodium, at 0.1 mM, inhibited significantly O^-_2 generation in rat PMN induced by opsonized zymosan. At 0.5 mM, diclofenac sodium and indomethacin inhibited the O^-_2 generation in rat PMN. All of the above drugs slightly inhibited O^-_2 production by the xanthine-xanthine oxidase system. On the other hand, O^-_2 production by the NADPH-NADPH oxidase system was significantly inhibited by the addition of amfenac sodium, ketoprofen or indomethacin. These results suggest that non-steroidal anti-inflammatory drugs do not work as an O^-_2 scavenger and block O^-_2 production by the NADPH-NADPH oxidase system of rat PMN. It is concluded that amfenac sodium and the other drugs are able to inhibit granulocyte O^-_2 production by blocking the activation of NADPH-oxidase.
社団法人日本薬学会の論文
1991-04-25